Obstetrics and Gynecology - A. M. Gromova 2000

Menstrual Function Disorders
Forms of Menstrual Cycle Disorders
Dysfunctional Uterine Bleeding (DUB)

Dysfunctional uterine bleeding (DUB) refers to bleeding caused by disruptions in the cyclic secretion of Hormones regulating the Menstrual cycle, in the absence of pronounced anatomical Changes in the Reproductive System. DUB can occur in girls (juvenile bleeding), women of reproductive age, and during the menopausal transition. It is often triggered by nervous exhaustion, psychological trauma, extragenital disorders—particularly infectious diseases—metabolic disturbances, infantilism, endocrine disorders, poor Nutrition, intoxication, Vitamin C and K deficiencies, coagulation disorders, or prior gynecological conditions (such as inflammation or uterine malposition).

Based on their Pathogenesis, uterine bleedings are classified into ovulatory (occurring in the presence of ovulation, where one of the cycle phases is shortened or prolonged) and anovulatory (occurring in the absence of ovulation).

Ovulatory Uterine Bleeding

This form of DUB is characterized by the presence of ovulation, albeit with disrupted rhythmicity in ovarian hormone secretion.

There are 3 main variants of this pathology:

1. Shortening of the follicular phase of the cycle.

2. Shortening of the luteal phase of the cycle.

3. Prolongation of the luteal phase of the cycle.

Additionally, ovulatory intermenstrual bleeding belongs to this group of menstrual cycle disorders.

Shortening of the follicular phase with a preserved luteal phase is caused by pituitary dysfunction. Such disorders most commonly occur during Puberty when menstrual function has not yet fully stabilized. In these cases, the follicular phase lasts only 7-8 days due to accelerated follicular maturation and early ovulation, reducing the total cycle length to 14-21 days. Women in this group experience menstruation more frequently than normal (proiomenorrhea), and the bleeding is prolonged and heavy (hyperpolymenorrhea). This occurs because the endometrium is insufficiently primed by progesterone During the first phase of the cycle; consequently, it fails to achieve the required degree of secretory transformation during the luteal phase and is shed in large sheets. Characteristic diagnostic signs include an early rise in basal body Temperature (on days 7-9 of the cycle) and a positive "fern" (pupil) sign. Histological examination of an endometrial biopsy taken on days 18-20 of the cycle reveals changes typical of a full-fledged secretory phase.

Hormonal therapy is typically not prescribed for such patients. Management is limited to symptomatic treatments (uterine contractility enhancers for hypermenorrhea, vitamin therapy, Blood clotting agents, and anti-anemia therapy). If this pathology is accompanied by Infertility, medium doses of estrogens (2-5 mg daily) may be administered on days 2, 4, and 6, or daily from days 2 to 10. Administered estrogens temporarily suppress FSH production, diminishing its impact on the Ovaries, which slows follicular maturation and delays ovulation. Synthetic progestins are prescribed for 2-3 cycles.

Shortening of the luteal phase is associated with atresia of the corpus luteum and represents the most frequent type of ovulatory bleeding. Luteal insufficiency is usually linked to impaired luteinizing and luteotropic Functions resulting from chronic inflammatory processes. Due to decreased progesterone production by the corpus luteum, the secretory phase turns out to be inadequate and short.

Clinically, this condition is marked by a shortened menstrual cycle and increased menstrual blood loss (proiomenorrhea, hyperpolymenorrhea). These women frequently suffer from functional infertility.

To diagnose a shortened luteal phase, the basal body temperature curve is analyzed (it remains elevated for only 4-6 days, and the temperature difference between the two cycle phases is less than 0.6°C). Progesterone levels are reduced (testing should begin no earlier than 4-5 days after the rise in rectal temperature). However, even normal levels do not guarantee a fully functional secretory phase, as endometrial receptor defects may be present. Therefore, in cases of infertility, an endometrial biopsy performed 2-3 days prior to menstruation is indicated, which reveals insufficient secretory transformation of the endometrium.

Treatment for luteal phase deficiency begins with progesterone replacement therapy initiated 10 days before the onset of the menstrual cycle, which helps prolong the second phase of the cycle. It should be noted that norsteroids (Orgametril, Primolut-N) possess a luteolytic effect. Prolongation of the luteal phase can also be achieved using human chorionic gonadotropin (hCG). Chorionic gonadotropin is administered at 1500-2000 IU on days 2, 4, and 6 of the basal temperature rise, or at 500 IU daily for 4-5 days post-ovulation. hCG administration can be combined with clomiphene or pergonal, provided that blood estradiol levels or ultrasound monitoring are utilized to prevent ovarian hyperstimulation syndrome. Combined estrogen-progestin medications are prescribed for 2-3 courses to achieve a rebound effect. For concomitant hyperprolactinemia, parlodel is used at 2.5-7.5 mg/day for 4-6 cycles, while hyperandrogenism is treated with dexamethasone at 0.25-0.5 mg/day.

Prolongation of the luteal phase of the menstrual cycle is caused by the persistence of a mature or immature corpus luteum amidst a normal first (follicular) phase. Persistence of a mature corpus luteum involves hyperproduction of progesterone, causing excessive endometrial proliferation prior to bleeding. Bleeding occurs on schedule or after a slight delay. With each successive cycle, the bleeding becomes more prolonged and heavy, occasionally lasting up to 1-1.5 months.

Functional diagnostic tests show a timely appearance of the "pupil" sign, followed by a sustained, significant rise in basal temperature to 37.3-37.5°C. Vaginal smears during the second phase display a high number of folded intermediate Cells. Histological analysis of an endometrial biopsy demonstrates a fully developed secretory phase.

Persistence of an immature corpus luteum results in minimal progesterone production, characterized by a slight basal temperature rise to 37-37.3°C, a low number (++) of folded intermediate cells in vaginal smears throughout the entire second phase, and an endometrium in a secretory state upon histological examination. Progesterone excretion is found to be adequate or elevated. Treatment for women with a prolonged second phase begins with hemostasis via uterine curettage, followed by The regulation of ovarian function using estrogen-progestin drugs such as oral contraceptives.

Ovulatory intermenstrual bleeding regularly occurs on days 10-12 following the end of menstruation and coincides temporally with ovulation.

Its onset is linked to a sharp drop in estrogen levels and altered sensitivity of endometrial receptors to these hormones. The spotting is usually light, painless, lasts 1-2 days, and may be accompanied by mild fatigue. The basal temperature is biphasic and within normal limits.

Treatment for ovulatory intermenstrual bleeding is indicated only in cases of significant blood loss and involves prescribing COMBINED ORAL CONTRACEPTIVES, 1 tablet daily from the 5th to the 25th day of the menstrual cycle for 3-4 months.

Anovulatory (Monophasic) Uterine Bleeding

These bleedings occur acyclically at intervals of 1.5-6 months and typically last longer than 10 days. Acyclic bleeding is caused by follicular persistence or atresia, whereas cyclic bleeding stems from short-term rhythmic follicular persistence. Acyclic bleedings are classified According to the patient's age.

Juvenile bleeding is characterized by a specific type of anovulation involving the atresia of a follicle that has not reached the ovulatory stage of maturity. This is attributed to the immaturity of hypothalamic-pituitary structures in puberty and their inability to rhythmically secrete GnRH and gonadotropins, which in turn disrupts ovarian folliculogenesis and leads to anovulation. Estrogen production is relatively monotonous yet prolonged, while progesterone is produced in minimal amounts. The stimulating effect of PGE₂ triggers endometrial proliferation; in The Setting of progesterone deficiency, the endometrium undergoes hyperplasia accompanied by glandular-cystic changes. Uterine bleeding results from stagnant hyperemia, capillary dilation, areas of necrosis, and uneven endometrial shedding. Contributing factors to prolonged bleeding include decreased uterine contractility associated with hypoplasia.

DUB in women of reproductive age most frequently arises from the persistence of mature follicles accompanied by excessive estrogen production. Ovulation fails to occur, a corpus luteum does not form, and a progesterone-deficient state coupled with absolute hyperestrogenism develops (unlike the relative hyperestrogenism seen in juvenile bleeding). Consequently, the duration and intensity of endometrial proliferation are extended. Hyperplastic changes (glandular-cystic hyperplasia) develop. Recurrent anovulation combined with hyperestrogenism carries an increased risk of developing Adenomatosis with atypical changes within the hyperplastic endometrium.

endometrium. The bleeding originates from areas of hyperplastic endometrium showing dystrophic changes, necrosis, and subsequent shedding. The excessive intensity and prolonged duration of these hemorrhages are driven by elevated levels of PGE and prostacyclin, which inhibit platelet aggregation and cause vasodilation.

Uterine bleeding in the premenopausal (Climacteric) period occurs due to age-related disruptions in the cyclic secretion of gonadotropins, follicular maturation, and ovarian hormonal function. This leads to luteal phase deficiency with corpus luteum dysfunction, which transitions into anovulatory ovarian dysfunction. It is typically characterized by relative hyperestrogenemia against a Background of absolute hypoprogesteronemia. The bleeding stems from hyperplastic endometrium containing foci of necrosis.

Hemorrhagic metropathy (prolonged follicular persistence, Schröder's disease) develops As a result of prolonged (2–6 weeks) persistence of a mature follicle. Ovulation does not occur, a corpus luteum fails to form, and the follicle undergoes continuous regression. The prolonged presence of the follicle is accompanied by excessive estrogen levels, triggering pathological proliferation with glandular-cystic endometrial hyperplasia, polypoid overgrowth, and impaired local blood supply. This leads to dystrophic changes, necrosis, and irregular desquamation. Bleeding is typically heavy, prolonged, and occurs after a 2–6-week delay in menstruation. Affected women suffer from infertility and dysfunction of other Organs and systems, while prolonged bleeding may lead to hypochromic anemia.

The condition can develop at various stages of life. Most commonly, it is observed in adolescent girls and during the menopausal transition.

Class="center">30.2.4.1. Diagnosis of AUB

When taking a medical history, special attention must always be paid to A number of factors that may contribute to menstrual irregularities: past childhood infections, extragenital diseases, endocrine disorders, Nervous system dysfunctions, infantilism, and adverse working and living conditions.

Cytology/practical/136.html">Differential diagnosis OF juvenile bleeding is carried out to rule out blood disorders accompanied by increased bleeding tendencies (thrombocytopenic purpura), hormonally active ovarian tumors, uterine myoma, Uterine Sarcoma, Cervical Cancer, and complicated Pregnancy. The diagnostic workup includes a detailed Analysis of the Blood Coagulation SYSTEM, ultrasound, and colposcopy using vaginal speculums suitable for adolescent girls. Estrogen, pregnanediol, and 17-KS levels in the urine are determined. Colpocytological studies and hormonal intradermal tests are also performed: 2 ml of folliculin is injected into one forearm, and 1.2 ml of a 0.5% progesterone solution into the other. Results are evaluated after 2 hours. The hormonal saturation of the body is assessed by comparing the size of the resulting papules or areas of hyperemia.

Differential diagnosis of AUB in reproductive-aged women is performed to distinguish it from complicated uterine pregnancy, placental polyp, submucosal and intramural uterine myoma, endometrial polyps, adenomyosis, endometrial cancer, Ectopic Pregnancy, and other conditions. A thoroughly taken medical history is of significant importance for establishing the correct diagnosis. Bleeding at a young age or recurrent pregnancy loss may serve as an indirect indicator of ovarian dysfunction with luteal phase deficiency. The main diagnostic stage involves fractional Diagnostic curettage of the cervical canal and uterine cavity mucosa, followed by histological examination. Hysteroscopy and ultrasound are also performed.

Climacteric AUB is differentiated from endometrial adenocarcinoma, myoma, polyps, adenomyosis, hormonally active ovarian tumors, etc. Fractional Curettage of the cervical canal and uterine mucosa, followed by histological examination of the obtained material, is a mandatory diagnostic and therapeutic step. It must be performed with the utmost care, maintaining high oncological vigilance. Hysteroscopy, hysterosalpingography, and ultrasound are also utilized in cases of climacteric bleeding.

In cases of menstrual irregularities, functional diagnostic tests of ovarian activity are mandatory. With persistent mature follicles, the basal body temperature is monophasic and consistently remains below 37°C, while the «pupil» and «fern» phenomena are positive (+++), and karyopyknotic index (KPI) and eosinophilic index (EI) values range between 60–100%. High estrogen secretion (greater than 50 µmol/day) and low pregnanediol excretion (less than 6 mg/day) are observed.

In follicular atresia, a persistently low basal body temperature is combined with weakly expressed «pupil» and «fern» phenomena (+), and the KPI and EI do not exceed 10–20%. Estrogen excretion is moderate (not exceeding 40 nmol/day), while pregnanediol excretion is reduced.

30.2.4.2. Treatment of AUB

Two main goals are set during treatment:

1. To stop the bleeding.

2. To prevent its recurrence.

In cases of juvenile bleeding, hemostasis can be achieved using hormonal agents or by uterine curettage. The choice of hemostatic method depends on the patient's general condition and the degree of blood loss. Patients who fail to respond to conservative treatment, as well as those experiencing prolonged heavy bleeding accompanied by weakness, dizziness, hypotension, tachycardia, Hemoglobin levels below 70 g/L, and a hematocrit of 20%, should undergo uterine curettage. To prevent damaging the hymen, it is infiltrated with a 0.25% novocain solution containing 640 IU of hyaluronidase. In other cases, hormonal hemostasis is performed.

For rapid hemostasis, estrogens are administered: 0.5-1 ml of a 0.1% sinestrol solution or 5000-10000 IU of folliculin intramuscularly every two hours until the bleeding stops, which typically occurs on the first day of treatment due to endometrial proliferation. In the following days, the daily dose of the medication is gradually reduced (by at least 1/3) to 1 ml of sinestrol or 10000 IU of folliculin, administered first in 2 doses, and then in 1 dose. Estrogen therapy is continued for 2-3 weeks, after which progestogens are introduced. Daily intramuscular injections of 1 ml of a 1% progesterone solution are given for 6-8 days, or 3-4 injections of 1 ml of a 2.5% progesterone solution every other day, or a single dose of 1 ml of a 12.5% 17-OHP solution. Alternatively, norkolut (10 mg daily) or turinal can be used.

In recent years, the best results in hormonal hemostasis have been achieved using combined estrogen-progestogen formulations containing 0.03-0.05 mg of estradiol (Non-ovlon, Rigevidon, Minisiston, Marvelon, Silest). They are prescribed 1 tablet 3-4 times a day. Once hemostasis is achieved, the dose is gradually reduced to 1 tablet per day. The course of treatment lasts 21 days. Menstruation-like bleeding begins 1-2 days after its completion. Starting from the 5th day of the new menstrual cycle, the same medications are taken at a dose of 1/2-1 tablet per day for 21 days. It is recommended to complete 3 courses of maintenance therapy.

Gonadotropin hemostasis is indicated for anovulatory bleeding (hyperestrogenism, luteal phase defect) in young women and girls according to Schmidt's regimen: 1000-2000 IU of choriogonadotropin daily until bleeding stops, followed by 500 IU every other day, with a total course dose of 6000-8000 IU.

In cases of minor bleeding (with a hemoglobin level above 100 g/L), non-hormonal hemostatic therapy may be used:

a) uterotonic agents — oxytocin, pituitrin, methylergometrine maleate solution (0.02%), ergotamine tartrate solution (0.05%), ergotal solution 0.05%, or methylergometrine solution (0.02%) — 1 ml intramuscularly or subcutaneously 1-2 times a day, or 1 ml by intravenous drip in 400 ml of 5% glucose solution;

b) hemostatic agents — calcium chloride or gluconate 10% – 10 ml intravenously; vicasol solution 1% – 1 ml intramuscularly twice a day; solution of ∑-aminocaproic acid 5% – 100 ml by intravenous drip or orally 2-3 g 3 times a day for 7-8 days; PAMBA 0.25 g orally 2-4 times a day; etamsylate (dicynone) solution 12.5% 2 ml 2-4 times a day intramuscularly or intravenously 4-6 times a day until bleeding stops, followed by oral tablets (1-2 tablets 3-4 times a day); ATP 1 ml intramuscularly (a course of 20-30 injections to improve platelet aggregation and uterine Muscle contractility). Fibrinogen (2-3 g intravenously), as well as dry or fresh-frozen plasma, is also used. Herbal hemostatics in the form of decoctions of stinging nettle, Water pepper, guelder rose, yarrow, great burnet, and shepherd's purse also aid in recovery.

Concurrently with surgical or hormonal hemostasis, active antianemic and general tonic therapy is administered, which includes:

- blood transfusions, packed red Blood Cells, and plasma when indicated;

- rheopolyglucukin infusion at a rate of 8-10 ml/kg, daily intramuscular injections of 1% ATP solution, 2 ml for 10 days;

- iron preparations: fercoven, ferroplex, femotek, ferrogradumet, ferrum-lek; hemosimulin at 0.5 g three times a day is used as a hematopoiesis stimulant and hemostatic agent;

- vitamin B₁₂ intramuscularly at 200 mcg daily with Folic acid at 0.01 g 2-3 times a day;

- 40% glucose solution 20 ml intravenously with 5% ascorbic acid – 3-5 ml, vitamin B₁ alternately with vitamin B₆ 1 ml intramuscularly for 10 injections;

- Vitamins E (50 mg) and A (33,000 IU) daily 50 mg orally for 1 month to stimulate ovarian function and endometrial regeneration; with a short break, the courses are repeated twice.

- in the presence of infectious and allergic diseases, antihistamines and agents that increase the immunological resistance of the body are prescribed: methyluracil, decaris, apilac, splenine, Beresh drops, thymolin, T-activin, echinacea;

- mexalin at 0.05 g 3 times a day for 5-7 days to stimulate pituitary function and normalize serotonin METABOLISM;

- physiotherapeutic treatment Methods: 2% copper sulfate solution in phase I of the cycle and 2% zinc sulfate solution in phase II as iontophoresis on the lower abdomen; cervical-facial galvanization with 1% zinc sulfate solution or 10% copper sulfate solution, 10% calcium chloride solution, 2-3% magnesium sulfate solution, or 2-3% sodium bromide solution; endonasal ionogalvanization with 2% Vitamin B1 solution for anovulatory hypoestrogenic bleeding, or with 0.25-0.5% novocaine solution for hyperestrogenic bleeding. The treatment course consists of 12-15 daily or alternate-day Procedures. During the period of menstrual delay to prevent relapses, vibratory massage of the paravertebral Zones of the lumbosacral spine is recommended. For the treatment of AUB, reflexotherapy, acupuncture, laser puncture, cold stimulation of the cervix receptors, and cervical electrical stimulation are also used.

The Second Stage of treatment for juvenile bleeding is the Prevention of recurrent bleeding. For this purpose, estrogen-progestogen drugs are prescribed from the 16th to the 25th day of the established menstrual cycle for 3-4 months. The Use of pure progestogens is possible: norkolut 5 mg from the 16th to the 25th day of the cycle, or 12.5% 17-OPC solution at a dose of 125 mg (1 ml) on the 17th and 21st days of the cycle for 3-4 months.

Treatment of AUB in women of reproductive age begins with diagnostic and therapeutic curettage of the uterine cavity walls. Surgical methods for treating AUB also include endometrial vacuum aspiration, destruction of the endometrium by freezing (cryodestruction), electrocoagulation, laser vaporization, Hysterectomy, omentovariosopexy, etc.

In case of recurrent bleeding when uterine curettage was performed less than 6 months ago, provided that histological examination results are favorable, hormonal hemostasis becomes necessary if the patient has not received anti-relapse therapy. Synthetic estrogen-progestogen preparations (rigevidon, ovidon, anovlar, non-ovlon) are used up to 6-8 tablets per day, daily reducing the dose by 1 tablet down to 1 tablet. The course of treatment is 21 days. Hemostasis can be performed using pure progestogens (pregnin at 60 mg daily or progesterone at 10 mg daily) or estrogen hemostasis (initially, 5 mg of estradiol dipropionate 50,000 IU is prescribed as a single intramuscular injection, then diethylstilbestrol in 5 mg tablets every 4 hours until bleeding stops). The latter is less favorable because the menstruation-like reaction that occurs after its withdrawal, in case of insufficient epithelial transformation, may be accompanied by rough desquamation and massive bleeding. Therefore, after hemostasis with estrogen preparations, progestogens must be prescribed.

After the cessation of bleeding, cyclic regulatory therapy with synthetic progestins, estrogens, and progesterone, or human chorionic gonadotropin and progesterone, is indicated.

Local hemostasis can be performed using a Thrombin sponge, CAC, or 1% adrenaline solution. A tampon is moistened with one of these solutions and inserted into the cervix for 8 hours.

Grammatikati's method is used in two variants:

1. Introduction of a 5% iodine solution into the uterine cavity using a Braun syringe. Start with 0.2 ml and add 0.1 ml daily, bringing it up to 1 ml (maximum 2-3 ml). The course of treatment is 20-30 days daily or every other day.

2. Tamponade of the Uterus with a tampon well soaked in a 5-10% iodine solution. Exposure time is 20-30 minutes. The course of treatment is 1-3 procedures. Histological verification of the diagnosis before treatment is mandatory.

After uterine curettage, patients are subject to follow-up dispensary monitoring and control of the menstrual cycle state using functional Diagnostics tests. When the phase pattern of the menstrual cycle is restored, no treatment is required. The appearance of anovulation is an indication for Hormonal Regulation of the cycle, taking into account the pathomorphology of the uterus and ovaries (considering functional diagnostic tests). Symptomatic therapy is carried out according to the same principle as in juvenile bleeding.

In the event of bleeding in climacteric women, to rule out precancerous conditions and tumors, treatment should begin with diagnostic fractional curettage of the cervical canal and the mucous membrane of the uterine cavity. For women under 48 years of age with glandular-cystic hyperplasia, 17-OPC is prescribed at 125-250 mg on the 14th, 17th, and 21st days after curettage, and its administration is then continued at the same dose on the same days of the cycle for 4-6 months. Norkolut is prescribed at 5-10 mg from the 16th to the 25th day of the cycle, also for 4-6 months. For women over 48 years of age, especially with recurrent hyperplasia, therapy aimed at suppressing menstrual function is recommended. They are prescribed 17-OPC at 250 mg in a continuous regimen twice a week for 6 months. It is preferable to use danazol at 400 mg daily or gestrinone at 5 mg twice a week for 4-6 months, which eliminate endometrial hyperplasia due to their antigonadotropic activity.

Androgen treatment is recommended for recurrent bleeding in women over 50 years of age who have hypoplastic atrophic changes in the endometrium revealed histologically. Long-acting androgens are used: omnadren or sustanon-250 once a month, or testenat 1 ml of a 10% solution twice a month for 3-4 months.

Correction of metabolic and endocrine disorders—such as obesity, hyperglycemia, and Hypertension—is mandatory.

Surgical intervention (supravaginal amputation or hysterectomy) is performed according to the following indications:

1. Absolute:

- endometrial adenocarcinoma;

- atypical endometrial hyperplasia combined with adenomatosis;

- uterine myoma of various localizations;

- enlargement of the ovaries;

- submucosal Location of uterine fibroids;

- nodular form of adenomyosis;

- combination of adenomyosis with uterine fibroids in the absence of Endometrial Hyperplastic Processes.

2. Relative:

- recurrent glandular-cystic hyperplasia;

- recurrent polyps in women with metabolic and endocrine disorders.

Control Questions

1. What uterine bleeding is referred to as dysfunctional?

2. What are follicular persistence and atresia?

3. How does bleeding occur in follicular persistence?

4. How does bleeding occur in follicular atresia?

5. What forms of biphasic uterine bleeding are distinguished?

6. How to diagnose menstrual cycle disorders in biphasic bleeding?

7. How to diagnose a shortened luteal phase?

8. How to diagnose a prolonged luteal phase?

9. How to diagnose the absence of ovulation?

10. What is the result of endometrial histological examination in Schröder's hemorrhagic metropathy?

11. Management of patients with uterine bleeding at various ages.

12. What is estrogen hemostasis?